Wu Ping, Zuo Xialin, Ji Aimin
Center of New Drug Research and Development, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, P.R. China.
Exp Ther Med. 2012 Apr;3(4):571-576. doi: 10.3892/etm.2012.452. Epub 2012 Jan 31.
Stroke is one of the leading causes of death and disability worldwide. In past decades, researchers have studied the physiopathology and biochemistry of stroke, but knowledge of the molecular mechanisms underlying this disease remains at an early stage. To date, only recombinant tissue plasminogen activator (rtPA) has been approved by the USA FDA for acute ischemic stroke. However, as the limiting therapy time window is 4.5 h after stroke onset and patients must meet the applicable conditions, a small number of patients benefit from this therapy. Therefore, the research and development of new drugs for stroke are a big challenge for scientists. MicroRNAs (miRNAs) are short (20-23 nucleotides) single-stranded non-coding RNAs. The seed sequences at positions 2-7 from the 5' end which are partially or complementary to one or more mRNAs inhibit or degrade target mRNAs, thus playing an important role in the post-transcriptional regulation of gene expression. Disregulated miRNAs have revealed their complex role in pathophysiological processes, and have also shown their potential role in disease diagnosis, and use as drug targets in neurodegenerative diseases and cancer. Recently, studies have found aberrantly expressed miRNAs in stroke; however, the implication of deregulated miRNA expression in stroke remains largely unknown. This review briefly summarizes recent studies concerning miRNA expression in stroke in vivo and in vitro, focuses on aberrant miRNA expression, as well as discusses their potential therapeutic role for stroke.
中风是全球范围内主要的死亡和致残原因之一。在过去几十年中,研究人员对中风的生理病理学和生物化学进行了研究,但对该疾病潜在分子机制的了解仍处于早期阶段。迄今为止,只有重组组织型纤溶酶原激活剂(rtPA)已被美国食品药品监督管理局(FDA)批准用于急性缺血性中风。然而,由于中风发作后限制治疗的时间窗为4.5小时,且患者必须符合适用条件,因此只有少数患者能从这种治疗中获益。因此,研发治疗中风的新药对科学家来说是一项巨大的挑战。微小RNA(miRNA)是短(20 - 23个核苷酸)的单链非编码RNA。其5'端第2 - 7位的种子序列与一个或多个mRNA部分互补或完全互补,可抑制或降解靶mRNA,从而在基因表达的转录后调控中发挥重要作用。失调的miRNA已在病理生理过程中显示出其复杂作用,并且在疾病诊断以及作为神经退行性疾病和癌症的药物靶点方面也显示出其潜在作用。最近,研究发现中风中存在异常表达的miRNA;然而,miRNA表达失调在中风中的意义仍 largely未知。本综述简要总结了近期关于体内和体外中风中miRNA表达的研究,重点关注异常的miRNA表达,并讨论了它们对中风的潜在治疗作用。 (注:“largely”原英文有误,推测可能是“largely”,翻译为“在很大程度上” )